The following letter has been sent today by José Luis Castro, Executive Director, The Union, to Dr. Margaret Chan, Director-General, World Health Organization (WHO).

This is in response to the WHO statement that tuberculosis (TB) has not been included in the Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics, published 27 February 2017.

The Union demands TB be included in the WHO lists of bacteria for which new antibiotics are urgently needed. Drug-resistant TB is a leading cause of sickness and death. Not including TB on this list is contrary to the available data and undermines efforts to find new and better treatments desperately needed by patients. This is particularly important for countries where drug-resistant TB has reached epidemic proportions.

The letter is reproduced in full below.

Dear Dr. Chan,

We are writing to you in strong protest of the fact that tuberculosis was left off—in fact, was not even considered for inclusion within—WHO’s first-ever Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics, published 27 February 2017.

Given the parameters laid out within the global PPL itself, as well as within WHO’s public messaging in release of the document, the choice to leave TB out of consideration is completely unjustified. Moreover, it is highly likely to have tangible, harmful effects on the urgent pursuit of new antibiotics for treating TB and drug-resistant TB.

The global PPL is described as exactly that: a global priority list of bacteria for which the world most urgently needs to accelerate basic science and R&D, leading to new antibiotics. Nowhere does the document state that the list applies to “orphan” pathogens or diseases that are relatively neglected. Rather, the global PPL describes its scope as being simply to “identify the most important resistant bacteria at a global level for which there is an urgent need for new treatments” (emphasis added).

The global PPL’s methodology was designed to all but eliminate subjective judgment within the process of categorising bacteria toward identifying which are highest priority. Using a multi-criteria decision analysis (MCDA) technique, the methodology’s main strength is said to be “the relatively high weight given to the evidence retrieved and summarised for each criterion in order to reduce the impact of individual perceptions and beliefs” (emphasis added).

It is outrageous, then, that Mycobacterium tuberculosis was left out of consideration, for the reason that “it is already a globally established priority for which innovative new treatments are urgently needed.” In other words, TB was not considered for inclusion in a global priority list, because it is evidently a global priority. This explanation defies reason. Moreover, it contradicts the stated intent of the global PPL’s methodology to define the list based on objective evidence, which includes the following:

M. tuberculosis kills more people than any other bacteria, and the global TB burden is increasingly characterised by drug-resistant forms. In 2015, an estimated 580,000 people were reported to have become sick from drug-resistant TB.

Since 2006, at least 100 countries have reported cases of extensively drug-resistant TB.

The only way of treating TB is with antibiotics. Current DR-TB treatments are arduous and cause terrible adverse effects including hearing loss and psychosis, as well as practical difficulties for families, communities, health systems and livelihoods.

TB R&D has been systematically underfunded during the previous decade. From 2011-2015, TB research received merely a third of the funding need identified by the Global Plan to Stop TB 2011-2015.

TB research funding has declined for the past two years, dropping by approximately US$53 million in 2015. TB research is now being funded at a lower point than it was at the height of the Great Recession.[1]

Only two new anti-TB antibiotics (bedaquiline and delamanid) have come to market since the mid-1960s, and the use of both medicines is currently limited to the most severely resistant cases.

The document’s stated intention to direct the flow of research funding means that TB’s exclusion could have tangible, harmful effects on TB research. This broadside comes at a critical time for tuberculosis advocacy, with G20 health leaders, the First WHO Global Ministerial Conference on Ending TB in the Sustainable Development Era, and the first-ever United Nations High Level Meeting on Global Tuberculosis all set to discuss a response to the challenge of drug-resistant TB. The nature and scope of the commitments announced at these gatherings are the outcome of intensive negotiations and advocacy. The leaders present at these gatherings have every reason to refer to the new global PPL when determining how to respond to the drug-resistant TB crisis, and then to weaken those commitments. We cannot rely on a footnote to prevent this scenario from unfolding.[2]

The global PPL includes 10 criteria the authors used to classify the families of bacteria on the list: all-cause mortality, healthcare and community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in hospital and community settings, treatability and current pipeline. M. tuberculosis would be likely to score highly for inclusion on the list based on every one of these 10 criteria.

TB’s exclusion sends the false and counterproductive message that drug-resistant TB is not an urgent public health threat. While the global PPL states (on page 6, deep within the document) that it “was not developed to identify public health threats,” this statement is flatly contradicted by the first sentence of the WHO news release issued to announce its publication: “WHO today published its first ever list of antibiotic-resistant ‘priority pathogens’—a catalogue of 12 families of bacteria that pose the greatest threat to human health.” The news release, in line with the document’s advocacy intent, then describes the global PPL as a “new tool to ensure R&D responds to urgent public health needs.”

Using subjective measures that disregard clear evidence, and with public messaging that contradicts the text of the document itself, the current design and promotion of the global PPL is sending a clear and strong advocacy message directly to policymakers worldwide: deprioritise TB research.

We urgently call on WHO to facilitate a timely review of M. tuberculosis for inclusion within the global PPL. As the document states, the global PPL was developed “in a way that allows periodic revisions and the inclusion of other pathogens.” This review should be conducted with time to include its findings within the “full protocol and results” to be published on the WHO website by the end of May 2017.

None of this is to say that M. tuberculosis should displace any of the 12 families of bacteria included in the global PPL. The global PPL is an important and potentially powerful tool for calling attention to antimicrobial resistance and for advocating for increased investment in the research and development of new antibiotics. WHO and the authors of the global PPL deserve praise for initiating the exercise. Given the immense burden of drug-resistant TB, the dire need for new treatment regimens, and the weak investment climate for TB research, M. tuberculosis must be reviewed for inclusion on the global PPL as soon as possible.